Angiogenesis is a necessary process for continued tumor growth and provides a convenient method for tumor metastasis. Tumors utilize the host's vascular system to direct new blood vessel formation from the host to the tumor. The process requires endothelial cell division and endothelial cell migration from the existing blood vessel to the tumor mass. Over the past several years, processes critical to angiogenesis have been identified. One of these is the enzyme methionine aminopeptidase 2 (MAP-2), an enzyme pivotal in endothelial cell division. Others have described small molecules capable of inhibiting this enzyme and preventing tumor angiogenesis in experimental systems. These molecules are all microbially derived. The goal of our research is to assess the ability of our novel sources of microbes- the deep subsurface of the Earth- for their ability to produce small molecule that inhibit MAP-2 and then develop these molecules into clinical entities. To accomplish this goal we have developed a progressive, interactive bioassay-chemical isolation protocol that will enable us to effectively identify and prioritize molecules for continued pre-clinical and clinical development. The goal of the Phase 1 grant is to provide proof of principle that our unique microbes produce such molecules and that we can isolate such molecules from microbial broths in sufficient quantities to perform continued drug discovery activities in Phase 2 studies. PROPOSED COMMERCIAL APPLICATION: Cancer is the number 2 killer of Americans. Metastasis is the primary cause of death in cancer. The development of an effective anti-angiogenesis drug would have a dramatic effect on our ability to treat and control cancer. The market would be immense.